The measurement of physical, chemical, biochemical and/or biological processes, such as reactions, binding and annealing processes and other interactions of particles with surfaces are of particular interest in the fields of quality control, drug discovery, medicine, basic research and molecular diagnostics. For analyzing these processes, methods, such as reflectrometric interference spectroscopy (RIfs), bio-layer interferometry (BLI), surface plasmone resonance (SPR), quartz crystal microbalance (QCM), surface acoustic wave (SAW), enzyme linked immunosorbent assay (ELISA), or even nanopores or transistors (next generation sequencing), are used.
Further exemplary methods include fluorescence measurements, fluorescence anisotropy measurements, Forster resonance energy transfer (FRET) measurements, total internal reflection fluorescence microscopy (TIRFM), backscattering interferometry (BSI), absorption, spectroscopy, AlphaScreen® assays, microscale thermophoresis (MST), patch clamp measurements.
Preferably, the particles to be analyzed are provided in a liquid, preferably in an aqueous solution. Surface-based methods are generally dependent on that the particles to be analyzed can reach the surface of the liquid or the surface of a sample chamber for an extended period of time, i.e. the measurement period and/or the incubation time or process time. In view of the finite concentration of the particles in the liquid and of the limited diffusion constant (diffusion rate) of the particles, a so-called “depletion layer” (see e.g. J. Mol. Recognit. 1999; 12:293-299) frequently forms at the surface and/or the boundary surface. This depletion layer may lead to a distortion of the measurement results and/or to a slowdown of the reaction and/or of analysis at the surface. Accordingly, in specific applications, e.g. the measurement of the koff rate (dissociation rate), where it is measured how and how fast the particles previously bound to the surface (e.g. antibodies) dissociate themselves therefrom and form a “concentration layer” of the dissociating particles. This concentration layer may cause an undesirable so-called “re-binding” of the dissociating particles. Both the depletion layer and the concentration layer may cause a distortion of the measurement results for the following reasons:                a) Binding (measurement of the binding rate/binding kinetics), depletion layer interfers.                    Here, a solution consisting of a buffer and dissolved/dissociated particles A of concentration [A] to be analyzed is introduced into the sample chamber. The binding kinetics are expressed by the rate gamma. γ=kon*[A]+koff, i.e. when particle A-containing buffer is added, the binding rate (association rate) kon cannot be measured independently of the dissociation rate koff. It is only possible to measure an apparent rate gamma, which, however, is dependent on the concentration [A]. However, it is frequently necessary to determine the concentration-independent rates kon and koff. Therefore, b) is necessary, too.            In a), the depletion layer interferes (binding, association); in b), the concentration layer interferes (dissociation).                        b) Measurement of dissociation/dissociation rate koff, concentration layer interfers (see, for example, also “Blocking rebinding with soluble receptor” in J. Mol. Recognit. 1999; 12:293-299).        Since, as described in a), it is not possible to measure kon and koff independently of each other, a second experiment is required with which it is possible to individually determine koff and then, together with a) or a repeated measurement of a) at different concentrations [A], to determine kon.        
Here, only the buffer, without particle A, is given into the sample chamber in which previously the binding of A was measured. In the sample chamber, A is present and bound to the surface. Attempts are then made to wash A away or to dissociate it so as to be able to measure the pure koff of A. Thus, if pure buffer is given into a sample chamber wherein A is bound to the surface (or bound to the molecules B immobilized there), then a new chemical equilibrium must be reached (the previous chemical equilibrium was reached for an A-containing buffer), which causes dissociation of the molecules A. If the dissociating molecule A is transported off rapidly enough, it cannot bind again to the surface (this would lead again to the measurement of gamma, i.e. kon and koff at the same time) and it is therefore possible to measure the pure koff rate. If A is not transported off rapidly enough, a concentration layer is formed. The values kon and/or koff are usually expressed by the units: kon: 1/([s]*[M]) and/or koff: 1/[s].
With known methods it is attempted to reduce the depletion layer and/or the concentration layer through a constant liquid flow, which is produced, for example, by external pumps. This approach has the considerable disadvantage that through the external pumps, valves and/or tubes a large dead volume is created, and that the whole system is rather error-prone. In addition, leaks, contamination of the tubes and valves, and cross-contamination through old samples which could not be completely removed may cause further measurement errors. Since to users often only very little or very expensive sample material is available, the above discussed dead volumes are a considerable economic disadvantage. Moreover, mostly apparatuses that are rather large/voluminous and difficult to transport are advantageous for controlling and regulating the pumps and valves and thus the liquid flow. This may prevent, inter alia, their use in “point of care”/“point of need” diagnostics.
Another method with which a depletion layer is to be prevented, moves or “shakes” the sample chamber macroscopically vis-à-vis a surface sensor. However, one problem with this method is that the sample chamber must be open towards the outside, so that the aqueous solution may evaporate and/or be contaminated by external influences. The mechanical “shaking” of the open sample chamber is also problematic since this shaking may cause liquids to overflow/“spill over” so that they may also infiltrate adjacent open sample chambers.
In addition, reference is made to German patent specification DE 103 25 307 B3 disclosing a method for mixing liquids in a microcavity by utilizing sound-induced flows.
It is an object of the present invention to reduce or overcome, in particular, the above-mentioned disadvantages of the prior art and to provide a new, preferably more advantageous method as well as a corresponding apparatus and system.